Design of Eu3+-Doped Fluoride Phosphor with Zero Thermal Quenching Property Based on Density Functional Theory.

Although being applied in various fields, white light emitting diodes (WLEDs) still have drawbacks that urgently need to be conquered: the luminescent intensity of commercial phosphors sharply decreases at working temperature. In this study, we calculated the forming energy of defects and confirmed that the VNa defect state can stably exist in ß-NaGdF4, by density functional theory (DFT) calculation. Furthermore, we predicted that the VNa vacancies would provide a zero thermal quenching (ZTQ) property for the ß-NaGdF4-based red-light phosphor. Then, a series of ß-NaGdF4:xEu3+ and ß-NaGdF4:0.25Eu3+,yYb3+ red-light phosphors were synthesized by the hydrothermal method. We found that ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+ phosphors possess ZTQ properties at a temperature range between 303-483 K and 303-523 K, respectively. The thermoluminescence (TL) spectra were employed to calculate the depth and density of the VNa vacancies in ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+. Combining the DFT calculation with characterization results of TL spectra, it is concluded that electrons stored in VNa vacancies are excited to the exited state of Eu3+ to compensate for the loss of Eu3+ luminescent intensity. This will lead to an increase of luminescent intensity at high temperatures and facilitate the samples to improve ZTQ properties. WLEDs were obtained with CRI = 83.0, 81.6 and CCT = 5393, 5149 K, respectively, when phosphors of ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+ were utilized as the red-light source. These results indicate that these two phosphors may become reliable red-light sources with high antithermal quenching properties for WLEDs.

Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer.

BACKGROUND: Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized. RESULTS: Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model. CONCLUSIONS: Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.

Research Progress on Cu-15Ni-8Sn Alloys: The Effect of Microalloying and Heat Treatment on Microstructure and Properties.

Cu-15Ni-8Sn alloy is the best choice to replace beryllium bronze alloy. This alloy has unparalleled application value in aerospace, ocean engineering, electronic information, equipment manufacturing, and other fields. However, the application of Cu-15Ni-8Sn alloy is challenged and limited because of a series of problems in its preparation and processing, such as easy segregation, difficult deformation, and discontinuous precipitation. It is an effective way to improve the comprehensive properties of Cu-15Ni-8Sn alloy using alloying design and process optimization to control the as-cast, deformed, and heat-treated microstructures. At present, it is a hot spot for scholars to study. In this paper, the grade generation, system evolution, and preparation technology development of Cu-15Ni-8Sn alloy are comprehensively reviewed. The phase transformation sequence of the Cu-15Ni-8Sn alloy is discussed. The influence of the type, amount, and existing form of alloying elements on the strength of Cu-15Ni-8Sn alloy and its mechanism are systematically summarized. Furthermore, the latest research progress on the effects of solid solution, cold deformation, and aging on the phase structure transformation and mechanical properties of Cu-15Ni-8Sn alloy is summarized. Finally, the future development trend of the Cu-15Ni-8Sn alloy is projected. The research results of this paper can provide a reference for the control of the microstructure and properties of high-performance Cu-15Ni-8Sn alloys used in key fields, as well as the optimization of the preparation process and alloy composition.

Efficacy and safety of Chinese herbal medicines combined with cyclophosphamide for connective tissue disease-associated interstitial lung disease: A meta-analysis of randomized controlled trials.

Objectives: To evaluate the effectiveness and safety of Chinese herbal medicines (CHMs) combined with cyclophosphamide (CTX) for connective tissue disease-associated interstitial lung disease (CTD-ILD) by performing a meta-analysis. Methods: We searched RCTs of Chinese herbal medicines therapy for connective tissue disease-associated interstitial lung disease in ten databases. Methodological quality assessment was performed by the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist. Results: Overall, seven RCTs with 506 participants were included for this analysis. Current data indicated that Chinese herbal medicines combined with cyclophosphamide contributed to a betterment in improving the clinical efficacy rate of connective tissue disease-associated interstitial lung disease [risk ratio (RR) = 1.21, 95% confidence interval (CI): (1.09, 1.35), p = 0.0003], tended to benefit improvement of lung function, which included VC [weighted mean difference (WMD) = 9.49, 95% CI: (5.54, 13.45), p < 0.00001], FVC [standardized mean difference (SMD) = 0.83, 95% CI: (0.36, 1.29), p = 0.0005], FEV1 [SMD = 0.54, 95% CI: (0.23, 0.86), p = 0.0008], TLC [SMD = 0.90, 95% CI: (0.68, 1.13), p < 0.00001], DLCO [SMD = 1.05, 95% CI: (0.38, 1.73), p = 0.002], and MVV [SMD = 0.83, 95% CI: (0.50, 1.17), p < 0.00001], and it also could significantly reduce the HRCT integral of lungs [SMD = -2.02, 95% CI: (-3.14, -0.91), p = 0.0004] and the level of ESR [WMD = -13.33, 95% CI: (-18.58, -8.09), p < 0.00001]. Furthermore, there was no statistical significance in the incidence of adverse events (AEs), which indicate that Chinese herbal medicines combined with cyclophosphamide is safe and does not increase adverse events compared with cyclophosphamide alone. Conclusion: Our analysis indicates that Chinese herbal medicines combined with cyclophosphamide may be a more effective strategy on the treatment of connective tissue disease-associated interstitial lung disease in the clinic. Because it included studies with relatively small sample size, the results need to be confirmed by more well-designed and large-scale RCTs. Systematic Review Registration: https://10.37766/inplasy2022.12.0010.

Efficacy of Bushen Jiangu therapy in the treatment of glucocorticoid-induced osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Bushen Jiangu (BSJG), a classic traditional Chinese medicine (TCM) therapy, is widely used for treatment of GIOP. We conducted a meta-analysis to evaluate the effectiveness and safety of BSJG therapy on the treatment of GIOP. METHODS: We searched randomized controlled trials (RCTs) of BSJG therapy for GIOP in 10 databases. Methodological quality assessment was performed by using the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist. RESULTS: Overall, 14 RCTs with 988 participants met the inclusion criteria. Pooled results indicated that BSJG therapy contributed to a betterment in improving the clinical efficacy rate of GIOP (risk ratio [RR] = 1.22, 95% confidence interval [CI]: 1.14, 1.30, P < .00001). The pooled results also indicated that BSJG therapy increased lumbar spine bone mineral density (LS-BMD) (weighted mean difference [WMD] = 0.21, 95% CI: 0.08, 0.33, P = .001), total hip bone mineral density (TH-BMD) (WMD = 0.16, 95% CI: 0.09, 0.24, P < .0001), and femoral neck bone mineral density (FN-BMD) (WMD = 0.07, 95% CI: 0.03, 0.10, P = .0001). Furthermore, our results indicated that BSJG therapy improved visual analogue scale (VAS) score (WMD = -0.60, 95% CI: -0.97, -0.23, P = .002), parathyroid hormone (PTH) (standardized mean difference [SMD] = -0.93, 95% CI: -1.58, -0.27, P = .006), and N-terminal propeptide of type I precollagen (PINP) (SMD = 0.69, 95% CI: 0.44, 0.95, P < .00001). In terms of safety, there was no significant difference in the adverse events (AEs) between the 2 groups (RR = 1.45, 95% CI: 0.63, 3.31, P = .38). CONCLUSION: Our analysis indicates that BSJG therapy has a valid and safe effect on the treatment of GIOP in the clinic. However, the results need to be confirmed in more well-designed and large-scale RCTs.

Effect of Mo on the Microstructures and Mechanical Properties of the Polycrystalline Superalloy with High W Content.

The effect of the Mo contents of 1.0 wt.%, 1.5 wt.%, 2.0 wt.%, and 3.0 wt.% on the microstructures and mechanical properties of the polycrystalline superalloy with a high W content was studied. The typical dendrite morphology was observed in the high-W superalloy with different Mo contents, containing γ matrix, γ' phase, eutectic, and MC carbide. After the heat treatment, the primary MC carbides were decomposed into M6C carbides, while a needle-like topologically close-packed (TCP) phase was formed in the alloy with high Mo content, in contrast to the other three alloys with low Mo content. The Mo addition increased the lattice parameter of the γ and γ' phases and also changed the lattice misfits of the γ and γ' phase lattice misfits towards a larger negative. The addition of Mo improved the yield strength at room temperature due to the solid solution strengthening and coherency strengthening. The improvement of the stress rupture lives at 975 °C/225 MPa was due to the combination of the suppressed propagation of the microcracks by the carbides and a more negative misfit. When the Mo content reached 3.0 wt.%, the TCP phases formed and decreased the ultimate tensile strength and the stress rupture lives as a result.

The persuasive role of the past: Policy feedback and citizens' acceptance of information communication technologies during the COVID-19 pandemic in China.

How can the enforcement of policies in the past influence a society's future adoption of information communication technologies (ICTs)? In this paper, we tackle this question by exploring how past e-governance policies influence citizens' willingness to use the health QR code, which is a COVID-19 tracing app widely used in China's pandemic control. Past policies regarding smart-city development in China involve two aspects: the construction of electronic infrastructure and the applications of specific technologies. Empirical analysis based on a nationwide dataset in China suggests that past policies exhibit persuasive effects and influence citizens' acceptance of the health QR code. Specifically, e-governance applications in cities significantly enhance citizens' acceptance through the demonstration of their usefulness. However, the construction of e-governance infrastructure per se does not have the same impact on citizens' acceptance. By connecting citizens' acceptance of new technology with past e-governance policies, the study illustrates a nuanced policy feedback mechanism through which past policies can substantially reshape public opinion by policy outcomes.

¿Cómo puede la aplicación de políticas en el pasado influir en la futura adopción de tecnologías de la información y la comunicación (TIC) en una sociedad? En este documento, abordamos esta pregunta explorando cómo las políticas de gobierno electrónico anteriores influyen en la voluntad de los ciudadanos de usar el código QR de salud, que es una aplicación de rastreo de COVID­19 ampliamente utilizada en el control de la pandemia en China. Las políticas anteriores con respecto al desarrollo de ciudades inteligentes en China involucran dos aspectos: la construcción de infraestructura electrónica y las aplicaciones de tecnologías específicas. El análisis empírico basado en un conjunto de datos a nivel nacional en China sugiere que las políticas anteriores exhiben efectos persuasivos e influyen en la aceptación del código QR de salud por parte de los ciudadanos. Específicamente, las aplicaciones de gobierno electrónico en las ciudades mejoran significativamente la aceptación de los ciudadanos a través de la demostración de su utilidad. Sin embargo, la construcción de infraestructura de gobierno electrónico per se no tiene el mismo impacto en la aceptación de los ciudadanos. Al conectar la aceptación de las nuevas tecnologías por parte de los ciudadanos con las políticas anteriores de gobierno electrónico, el estudio ilustra un mecanismo matizado de retroalimentación de políticas a través del cual las políticas anteriores pueden remodelar sustancialmente la opinión pública mediante los resultados de las políticas.

Regulation of KDM5C stability and enhancer reprogramming in breast cancer.

Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.

LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca2+]i in Pulmonary Arterial Smooth Muscle Cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling and sustained increase in right ventricular systolic pressure. The molecular mechanisms behind PH development remain unclear. Here, a long noncoding RNA (lncRNA) attenuated by platelet-derived growth factor BB (PDGF-BB) was identified, and its functional roles were investigated in vitro and in vivo. Using RNA-sequencing data and rapid amplification of cDNA ends, an lncRNA neighboring the locus of ATPase plasma membrane Ca2+ transporting 4 (PMCA4) was identified and named lncPTSR. It is a highly conserved nuclear lncRNA and was downregulated in pulmonary arterial smooth muscle cells (PASMCs) with PDGF-BB stimulation or hypoxia induction. Gene interruption or overexpression assays revealed that lncPTSR negatively regulates rat PASMC proliferation, apoptosis, and migration. LncPTSR interruption in Sprague Dawley rats using adeno-associated virus type 9-mediated shRNA resulted in a significant increase in right ventricular systolic pressure and vascular remodeling in normoxic condition. LncPTSR knockdown also suppressed PMCA4 expression and attenuated the intracellular Ca2 + efflux of PASMCs in vitro and in vivo. Further studies suggest a complex crosstalk between lncPTSR and mitogen-activated protein kinase pathway: inhibition of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase abolishes the PDGF-BB-mediated lncPTSR downregulation, and lncPTSR plays a feedback regulation for mitogen-activated protein kinase-signaling molecules. The present study suggests that lncPTSR participates in pulmonary artery remodeling via modulating the expression of PMCA4 and intracellular Ca2 + homeostasis downstream of PDGF-BB-driven mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. These results suggest that lncPTSR may be a promising therapeutic target in PH treatment.

Inhibition of histone methyltransferase SETD8 represses DNA virus replication.

Multiple diseases, such as cancer and neural degeneration diseases, are related with the latent infection of DNA viruses. However, it is still difficult to clean up the latent DNA viruses and new anti-viral strategies are critical for disease treatment. Here, we screen a pool of small chemical molecules and identify UNC0379, an inhibitor for histone H4K20 methyltransferase SETD8, as an effective inhibitor for multiple DNA viruses. UNC0379 not only enhances the expression of anti-viral genes in THP-1 cells, but also repress DNA virus replication in multiple cell lines with defects in cGAS pathway. We prove that SETD8 promotes DNA virus replication in a manner dependent on its enzyme activity. Our results further indicated that SETD8 is required for PCNA stability, one factor critical for viral DNA replication. Viral infection stimulates the interaction between SETD8 and PCNA and thus enhances PCNA stability and viral DNA replication. Taken together, our study reveals a new mechanism for regulating viral DNA replication and provides a potential strategy for treatment of diseases related with DNA viruses.

Government responsiveness and public acceptance of big-data technology in urban governance: Evidence from China during the COVID-19 pandemic.

The COVID-19 global pandemic has posed unprecedented challenges to nations and cities worldwide. Governments have adopted Information and Communication Technologies (ICTs) to rapidly control the spread of a novel coronavirus. As an innovative but controversial ICT-based tool, health QR code plays a vital role by assisting rapid contact tracing. Yet, whether and how citizens accept this policy tool remains an unknown theoretical and empirical question. In this paper, we study the sources that determine citizens' acceptance of health QR code in city governance. Based on a nation-wide online survey covering 28 major provincial-capital cities in China, we find that individual experiences and political identities affect citizens' acceptance of QR code. Even though public opinion regarding this issue is diverse, the government's responses to citizens' requests play a critical role in enhancing their acceptance of using QR code both in the current and future stages. Specifically, as the citizens perceive a higher level of city government responsiveness, they are less worried about privacy leaks and more likely to perceive the effectiveness of health QR code in improving public health, thus resulting in a higher acceptance. The results offer broad policy implications for smart cities and urban governance.

PDGF/MEK/ERK axis represses Ca2+ clearance via decreasing the abundance of plasma membrane Ca2+ pump PMCA4 in pulmonary arterial smooth muscle cells.

Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by vascular remodeling and vasoconstriction, which is associated with increased intracellular calcium ion concentration ([Ca2+]i). Platelet-derived growth factor-BB (PDGF-BB) is the most potent mitogen for pulmonary arterial smooth muscle cells (PASMCs) and is involved in vascular remodeling during PAH development. PDGF signaling has been proved to participate in maintaining Ca2+ homeostasis of PASMCs; however, the mechanism needs to be further elucidated. Here, we illuminate that the expression of plasma membrane calcium-transporting ATPase 4 (PMCA4) was downregulated in PASMCs after PDGF-BB stimulation, which could be abolished by restraining the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK). Functionally, suppression of PMCA4 attenuated the [Ca2+]i clearance in PASMCs after Ca2+ entry, promoting cell proliferation and elevating cell locomotion through mediating formation of focal adhesion. Additionally, the expression of PMCA4 was decreased in the pulmonary artery of monocrotaline (MCT)- or hypoxia-induced PAH rats. Moreover, knockdown of PMCA4 could increase the right ventricular systolic pressure (RVSP) and wall thickness (WT) of pulmonary artery in rats raised under normal conditions. Taken together, our findings demonstrate the importance of the PDGF/MEK/ERK/PMCA4 axis in intracellular Ca2+ homeostasis in PASMCs, indicating a functional role of PMCA4 in pulmonary arterial remodeling and PAH development.

A novel tonicity-responsive microRNA miR-23a-5p modulates renal cell survival under osmotic stress through targeting heat shock protein 70 HSPA1B.

There is growing evidence that microRNAs (miRNAs) are implicated in cellular adaptation to osmotic stress, but the underlying osmosignaling pathways are still not completely understood. In this study, we found that a passenger strand miRNA, miR-23a-5p, was significantly downregulated in response to high NaCl treatment in mouse inner medullary collecting duct cells (mIMCD3) through an miRNA profiling assay. The decrease of miR-23a-5p is hypertonicity-dependent and osmotolerant cell type-specific. Knockdown of miR-23a-5p increased cellular survival and proliferation in mIMCD3. In contrast, miR-23a-5p overexpression repressed cell viability and proliferation under hypertonic stress. RNA deep-sequencing revealed that a heat shock protein 70 (HSP70) isoform, HSP70 member 1B (HSPA1B), was significantly increased under hypertonic treatment. Based on the prediction analysis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and TargetScan, and a further validation via a dual-luciferase assay, HSPA1B was identified as a potential target of miR-23a-5p. Overexpressed miR-23a-5p suppressed HSPA1B, whereas downregulated miR-23a-5p promoted HSPA1B expression in mIMCD3. In addition, an in vivo study demonstrated that there is a reverse correlation between the levels of miR-23a-5p and HSPA1B in mouse renal inner medulla (papilla) that is exposed to extremely high osmolality. In summary, this study elucidates that passenger strand miR-23a-5p is a novel tonicity-responsive miRNA. The downregulation of miR-23a-5p facilitates cellular adaptation to hypertonic stress in mammalian renal cells through modulating HSPA1B.

Classifier categories reflect but do not affect conceptual organization.

Do we structure object-related conceptual information according to real-world sensorimotor experience, or can it also be shaped by linguistic information? This study investigates whether a feature of language coded in grammar-numeral classifiers-affects the conceptual representation of objects. We compared speakers of Mandarin (a classifier language) with speakers of Dutch (a language without classifiers) on how they judged object similarity in 4 studies. In the first 3 studies, participants had to rate how similar a target object was to 4 comparison objects, 1 of which shared a classifier with the target. Objects were presented as either words or pictures. Overall, the target object was always rated as most similar to the object with the shared classifier, but this was the case regardless of the language of the participant. In a final study using a successive pile-sorting task, we also found that the underlying object concepts were similar for speakers of Mandarin and Dutch. Speakers of a nonclassifier language are therefore sensitive to the same conceptual similarities that underlie classifier systems in a classifier language. Classifier systems may therefore reflect conceptual structure, rather than shape it. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Optimized algorithm in solid thyroid nodule elastography.

The present study aimed to evaluate the reproducibility and accuracy of the optimized algorithm of shear-wave elastography (SWE) in diagnosing solid thyroid nodules. Two hundred and sixty-three solid thyroid nodules in 248 patients who underwent conventional ultrasound and SWE, respectively, by two operators were scheduled for fine-needle aspiration or surgery. Elasticity indices of the mean, minimum and maximum of nodules (EI) and thyroid parenchyma (EInorm) were measured respectively in the same frame of elastographic images for three times by both operators. The intraobserver and interobserver reproducibility of the optimized algorithm were assessed by intraclass correlation coefficients (ICC). Diagnostic performance of the optimized algorithm was compared with that of conventional SWE measurements by receiver-operating characteristic (ROC) curves. Among a total of 243 nodules included, 121 were benign nodules and 122 were papillary thyroid carcinoma (PTC). Intraobserver reliability for EId and EIr was nearly perfect (ICC>0.80). Interobserver agreement for MEANd, MAXd, MEANr and MAXr was nearly perfect (ICC>0.80). MAXd had the largest areas under the ROC curve which was 0.82. Compared with conventional SWE, the optimized algorithm of SWE shows better reproducibility and performance in diagnosing solid thyroid nodules.

Percutaneous sclerotherapy with polidocanol under the guidance of ultrasound for venous malformations in children - A retrospective cohort study from a single tertiary medical center.

This study reports our experience, the therapeutic outcomes and complications of percutaneous sclerotherapy (PS) with polidocanol to treat venous malformations (VMs) in children.A retrospective analysis was conducted of pediatric patients with VMs who underwent PS using polidocanol under continuous ultrasound (US) guidance between January 2015 and January 2018 at our department. Medical records were reviewed to record demographic information, lesion characteristics, treatment sessions, therapeutic outcomes and complications. χ analysis was employed to evaluate the effects of these characteristics on outcomes.Hundred treatment sessions were performed for lesions in 47 patients. The mean age of the patients was 4.1 ±â€Š3.6 years (mean ±â€ŠSD). The female to male ratio was almost 2:1 (female 32, male 15). The location of the VMs included the head and neck in 16 cases (34.0%), upper extremity in 11 cases (23.4%), lower extremity in 10 cases (21.3%), and trunk and perineum in 10 cases (21.3%). The majority of the lesions were focal in 36 cases (76.6%), while 11 (23.4%) were diffuse. Seventeen patients (36.2%) underwent single PS session, 14 patients (29.8%) underwent 2 sessions, 10 patients (21.3%) underwent 3 sessions and 6 patients (12.7%) underwent ≧4 sessions. The mean PS session per patient was 2.1 ±â€Š1.1. The mean follow-up duration was 11.4 ±â€Š7.6 months. After the last PS session, 8 patients (17.0%) had excellent outcomes, 27 (57.4%) had good outcomes, 10 (21.3%) had fair outcomes, and 2 (4.3%) had poor outcomes. Focal lesions were more likely to have good or excellent outcomes than diffuse lesions (χ = 4.522, P = .033). No other lesion characteristic significantly affected the outcomes (good or excellent outcomes), including lesion location (χ = 2.011, P = .570) or lesion size (χ = 1.045, P = .307). After the PS procedure, temporary local swelling occurred in 81 sessions (81.0%), local pain occurred in 15 sessions (15.0%), fever occurred in 27 (27.0%) sessions, and transient local numbness occurred in four sessions (4.0%).PS with polidocanol under the guidance of US appears to be safe and effective for the treatment of VMs in children, especially for focal lesions.

Pathobiology of pulmonary artery hypertension: role of long non-coding RNAs.

Pulmonary arterial hypertension (PAH) is a disease with complex pathobiology, significant morbidity and mortality, and remains without a cure. It is characterized by vascular remodelling associated with uncontrolled proliferation of pulmonary artery smooth muscle cells, endothelial cell proliferation and dysfunction, and endothelial-to-mesenchymal transition, leading to narrowing of the vascular lumen, increased vascular resistance and pulmonary arterial pressure, which inevitably results in right heart failure and death. There are multiple molecules and signalling pathways that are involved in the vascular remodelling, including non-coding RNAs, i.e. microRNAs and long non-coding RNAs (lncRNAs). It is only in recent years that the role of lncRNAs in the pathobiology of pulmonary vascular remodelling and right ventricular dysfunction is being vigorously investigated. In this review, we have summarized the current state of knowledge about the role of lncRNAs as key drivers and gatekeepers in regulating major cellular and molecular trafficking involved in the pathogenesis of PAH. In addition, we have discussed the limitations and challenges in translating lncRNA research in vivo and in therapeutic applications of lncRNAs in PAH.

PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells.

Platelet-derived growth factor (PDGF) can induce hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly downregulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGF receptor/PKCß signaling was found to repress miR-1181 expression. Then, gain- and loss-of-function experiments were respectively conducted and revealed the prominent role of miR-1181 in inhibiting PASMC proliferation and migration. Flow cytometry analysis suggested that miR-1181 regulated the PASMC proliferation through influencing the cell cycle transition from G0/G1 to S phase. Moreover, we exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate PASMC proliferation. Finally, serum miR-1181 expression was also observed to be reduced in adult and newborn patients with PAH. Overall, this study provides novel findings that the miR-1181/STAT3 axis mediated PDGFBB-induced dysfunction in human PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic candidate for the vascular remodeling diseases.

Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone Deacetylase 4 Regulatory Axis Mediates Platelet-Derived Growth Factor-Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells.

BACKGROUND: Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs found a significantly downregulated microRNA, miR-1281, but it has not been associated with any cellular function, and we investigated the possibility. METHODS AND RESULTS: Real-time quantitative reverse transcription-polymerase chain reaction assay proved that downregulation of miR-1281 was a conserved phenomenon in human and rat PASMCs. Overexpression and inhibition of miR-1281 in PASMCs promoted and suppressed, respectively, the cell proliferation and migration. Bioinformatic prediction and 3'-untranslated region reporter assay identified histone deacetylase 4 to be a direct target of miR-1281. Supporting this, proliferation and migration assay demonstrated the cellular function of histone deacetylase 4 is inversely correlated with that of miR-1281. Mechanistically, it is found that platelet-derived growth factor BB activates the phosphatidylinositol 3-kinase pathway, which then induces the expression of DNA methyltransferase 1, leading to enhanced methylation of a flanking CpG island and repressed miR-1281 expression. Finally, a reduced miR-1281 level was consistently identified in hypoxic PASMCs in vitro, in pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension, and in serum of patients with coronary heart disease-pulmonary arterial hypertension. These data suggest that there may be a diagnostic and therapeutic use for miR-1281. CONCLUSIONS: Herein, we report a novel regulatory axis, phosphatidylinositol 3-kinase-DNA methyltransferase 1-miR-1281-histone deacetylase 4, integrating multiple epigenetic regulators that participate in platelet-derived growth factor BB-stimulated PASMC proliferation and migration and pulmonary vascular remodeling.

The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells.

Pulmonary artery hypertension (PAH) is a rare and fatal disorder that involves extensive remodeling of the pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMCs; however, little is known about the role of long noncoding RNA (lncRNA) in this process. Using RNA sequencing, we identified 725 lncRNAs in rat PASMCs, 95 of which were expressed differentially in response to PDGF-BB treatment. Depletion of four lncRNAs affected the proliferation of rat PASMCs as measured by 5-ethynyl-2'-deoxyuridine incorporation assay. Among these, one lncRNA, named LnRPT (lncRNA regulated by PDGF and transforming growth factor ß), was found to be the most potent in promoting the proliferation of PASMCs when knocked down. In contrast, proliferation of PASMCs was repressed when LnRPT was overexpressed. Mechanistically, LnRPT inhibited the expression of two genes involved in the Notch signaling pathway (notch3 and jag1) as well as the cell-cycle-regulating gene ccna2. In addition, downregulation of LnRPT induced by PDGF-BB was abrogated when phosphatidylinositol 3'-kinase activity was inhibited with pictilisib. Downregulation of LnRPT was also observed in the pulmonary arteries of rats with monocrotaline-induced PAH. This study provides novel insights into the effects of PDGF-BB on lncRNA expression in PASMCs, and identifies one lncRNA, LnRPT, that plays a role in PAH development as a regulator of PASMC proliferation by mediating the Notch signaling pathway and cell cycle.